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Cross-neutralizing activity against SARS-CoV-2 variants in COVID-19 patients: Comparison of four waves of the pandemic in Japan

Koichi Furukawa1, Lidya Handayani Tjan1, Silvia Sutandhio1, Yukiya Kurahashi1, Sachiyo Iwata, Yoshiki Tohma, Shigeru Sano, Sachiko Nakamura, Mitsuhiro Nishimura1, Jun Arii1, Tatsunori Kiriu1, Masatsugu Yamamoto1, Tatsuya Nagano1, Yoshihiro Nishimura1, Yasuko Mori1 •
Kobe University1
13 Jun 2021-medRxiv (Cold Spring Harbor Laboratory Press)-
TL;DR: In this article, the neutralizing potency of 81 COVID-19 patients' sera from 4 waves of pandemic against SARS-CoV-2 variants using their authentic viruses was investigated.
Abstract: In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but is not firmly established. We investigated the neutralizing potency of 81 COVID-19 patients’ sera from 4 waves of pandemic against SARS-CoV-2 variants using their authentic viruses. Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351.

Summary (3 min read)

Jump to: [BACKGROUND] – [It is not yet known to what extent the serum of patients previously infected with] – [Diagnosis of COVID-19] – [Definitions of the waves of the COVID-19 pandemic in Japan] – [Participant recruitment] – [Measurement of neutralizing activity against SARS-CoV-2] – [Statistical analysis] – [Ethical approval] – [Patient characteristics] – [Neutralizing activity against all variants in all patients] – [Neutralizing activity against all variants in each wave] – [Neutralizing activity against each variant by severity] and [DISCUSSION]

BACKGROUND

  • The coronavirus disease 2019 (COVID-19) pandemic declared by the World Health Organization (WHO) in March 2020 continues to affect all countries around the world.
  • The emergence of these variants poses a tremendous challenge to the control of the SARS-CoV-2 pandemic.

It is not yet known to what extent the serum of patients previously infected with

  • Original SARS-CoV-2 might confer protection against these rapidly emerging variants.
  • This research might also help predict the potency of using plasma from individuals who recovered from the conventional type or All rights reserved.
  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted June 13, 2021.
  • MedRxiv preprint any variants of SARS-CoV-2 as a donor if convalescent plasma therapy can be used for COVID-19 patients infected by the other variants, also known as doi.

Diagnosis of COVID-19

  • COVID-19 diagnoses were based on the polymerase chain reaction (PCR) detection of the SARS-CoV-2 genome in nasopharyngeal swab samples.
  • Disease severity was defined as follows: Symptomatic COVID-19 cases without evidence of pneumonia or hypoxia were classified as mild.
  • Cases in patients with clinical signs of pneumonia were classified as moderate (oxygen saturation as measured by pulse oximetry, ≥90% with room air) or as severe (respirations >30/min, severe respiratory distress, or oxygen saturation <90% with room air).
  • Patients who needed mechanical ventilation were classified as critical.

Definitions of the waves of the COVID-19 pandemic in Japan

  • The period from the 1st wave to the 4th wave of the COVID-19 pandemic was defined based on the change in the number of infected people on a single day in Japan.
  • The 1st wave was from March 1st to the end of June 2020; the 2nd wave was from July 1st to All rights reserved.
  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted June 13, 2021.

Participant recruitment

  • From March 2020 to May 2021, blood samples were collected from patients who became infected with SARS-CoV-2 and were hospitalized at Hyogo Prefectural Kakogawa Medical Center (Hyogo, Japan).
  • The authors selected serum of convalescent patients with different disease severities who were already confirmed to have neutralizing activity against the SARS-CoV-2.
  • In May 2020, the serum of 24 healthy individuals were collected and confirmed to have no antibody against SARS-CoV-2; these sera were used as the negative control group [20] .
  • This study was a retrospective observational investigation and was carried out after written consent was obtained from the subjects or by the opt-out method when it was difficult to get written consent due to the disease severity.
  • No statistical methods were used to predetermine the sample size.

Measurement of neutralizing activity against SARS-CoV-2

  • Neutralization was performed as described [21] .
  • Briefly, the neutralizing activity of each serum sample was evaluated by a neutralization assay against each living All rights reserved.
  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The neutralizing antibody titer was determined as the highest serum dilution that did not show any cytopathic effects.

Statistical analysis

  • GraphPad Prism software (ver. 8.4.3) was used for the statistical analysis and preparation of figures.
  • The Friedman test was used to compare the neutralizing antibody titer among the four variants.
  • The Kruskal-Wallis test was used to compare the neutralizing antibody titer among different disease severity groups.
  • Results were considered significant at a p-value <0.05.

Ethical approval

  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • This study was approved by the ethical committees of Kobe University Graduate School of Medicine (approval code: B200200) and Hyogo Prefectural Kakogawa Medical Center.

Patient characteristics

  • The median number of days between the onset of symptoms and the collection of serum samples (days post-onset, dpo) was 26 days.
  • The asymptomatic/mildly infected group was comprised of 25 patients, 19 patients were moderate/severe, and the remaining 37 patients were in the critical infection group.
  • Eleven patients had received antiviral treatment with favipiravir or lopinavir (both for six patients and favipiravir for five patients), and 42 patients received steroid treatment.
  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Neutralizing activity against all variants in all patients

  • Most of the 81 sera had neutralizing activity against the four variants, although the activity values varied (Fig. 1 ).
  • The neutralizing titer of B.1.1.7 seemed to be higher than that of D614G, but the difference was not significant.

Neutralizing activity against all variants in each wave

  • From the 1st wave to the 3rd wave, the neutralizing activity against B.1.1.7 variant was similar or slightly low compared to that against D614G, whereas it was higher in the 4th wave (increased 4x, p = 0.0009).
  • In addition, the neutralizing activity against B.1.1.7 was also higher than that against P.1 or B.1.351 variant in the 4th wave.
  • In all waves, the neutralizing activity against B.1.351 variant was lower than those against the other All rights reserved.
  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted June 13, 2021.

Neutralizing activity against each variant by severity

  • The sera of all of the COVID-19 patients showed neutralizing activity against the D614G and B.1.1.7 regardless of the severity of the patients' symptoms.
  • Interestingly, almost all of the sera from the asymptomatic/mild infected group, with the exception of three cases, had neutralizing activity against all tested variants.
  • Three asymptomatic/mild cases and one case in the severe-infection group with low neutralizing activity against D614G (titer 8 or 16) did not show any neutralizing activity against P.1 or B.1.351 (Fig. 3c,d ).
  • This means that the neutralizing activities of sera from previously infected patients was also seen against the B.1.1.7 but All rights reserved.

DISCUSSION

  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted June 13, 2021.
  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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1
1
Cross-neutralizing activity against SARS-CoV-2 variants in COVID-19 patients:
2
Comparison of four waves of the pandemic in Japan
3
4
Koichi Furukawa, MD
1
*, Lidya Handayani Tjan, MD
1
*, Silvia Sutandhio, MD
1
, Yukiya
5
Kurahashi, MD
1
, Sachiyo Iwata, MD, PhD
2
, Yoshiki Tohma, MD
3
, Shigeru Sano, MD,
6
PhD
3
, Sachiko Nakamura, MD
4
, Mitsuhiro Nishimura, PhD
1
, Jun Arii, DVM, PhD
1
,
7
Tatsunori Kiriu, MD, PhD
5
, Masatsugu Yamamoto, MD, PhD
5
, Tatsuya Nagano, MD,
8
PhD
5
, Yoshihiro Nishimura, MD, PhD
5
, Yasuko Mori, MD, PhD
1
.
9
10
1
Division of Clinical Virology, Center for Infectious Disease, Kobe University Graduate
11
School of Medicine,
Kobe, Hyogo 650-0017, Japan
12
2
Division of Cardiovascular Medicine, Hyogo Prefectural Kakogawa Medical Center,
13
Kakogawa 675-0003, Japan
14
3
Acute Care Medical Center, Hyogo Prefectural Kakogawa Medical Center, Kakogawa
15
675-0003, Japan
16
4
Division of General Internal Medicine, Hyogo Prefectural Kakogawa Medical Center,
17
Kakogawa 675-0003, Japan
18
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 13, 2021. ; https://doi.org/10.1101/2021.06.10.21258682doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
2
5
Division of Respiratory Medicine, Department of Internal Medicine, Kobe University
1
Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
2
*Contributed equally to this work.
3
4
Corresponding author:
5
Prof. Yasuko Mori
6
Division of Clinical Virology, Center for Infectious Disease,
7
Kobe University Graduate School of Medicine.
8
7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo Japan, 650-0017
9
10
11
12
13
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 13, 2021. ; https://doi.org/10.1101/2021.06.10.21258682doi: medRxiv preprint
3
1
ABSTRACT
2
In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further
3
spread of infection, sera cross-neutralizing activity of patients previously infected with
4
conventional SARS-CoV-2 against novel variants is important but is not firmly
5
established. We investigated the neutralizing potency of 81 COVID-19 patients' sera
6
from 4 waves of pandemic against SARS-CoV-2 variants using their authentic viruses.
7
Most sera had neutralizing activity against all variants, showing similar activity against
8
B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave,
9
sera-neutralizing activity against B.1.1.7 was significantly higher than that against any
10
other variants, including D614G. The cross-neutralizing activity of convalescent sera
11
was effective against all variants but was potentially weaker for B.1.351.
12
13
Key Words: SARS-CoV-2, COVID-19, variant, reinfection, neutralizing activity
14
15
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 13, 2021. ; https://doi.org/10.1101/2021.06.10.21258682doi: medRxiv preprint
4
BACKGROUND
1
The coronavirus disease 2019 (COVID-19) pandemic declared by the World
2
Health Organization (WHO) in March 2020 continues to affect all countries around the
3
world. In efforts to control the pandemic, several vaccine platforms have been
4
developed based on the original severe acute respiratory syndrome coronavirus 2
5
(SARS-CoV-2) (Wuhan-1) as the template, and these vaccines have been shown to be
6
effective for reducing the COVID-19 outbreak [1-3].
7
However, the evolution of SARS-CoV-2 has continued since its initial emergence.
8
By the beginning of April 2020, a variant bearing a D614G mutation with evidence of
9
increased infectivity had become dominant [4]. The SARS-CoV-2 variant B.1.1.7, first
10
detected in Kent and Great London in September 2020, has now spread to many
11
countries worldwide with evidence indicating an increased mortality rate [5, 6]. In
12
addition to D614G and several mutations in other areas of the genome, B.1.1.7 bears
13
eight mutations in the spike gene including deletions in the N-terminal domain
14
(ΔH69/ΔV70, Δ144) and amino acid substitutions in the receptor binding domain
15
(N501Y) [7, 8].
16
The SARS-CoV-2 variant B.1.351 was first detected in specimens collected from
17
South Africa in October 2020, and it has rapidly become the predominant variant
18
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 13, 2021. ; https://doi.org/10.1101/2021.06.10.21258682doi: medRxiv preprint
5
circulating throughout South Africa [9]. Among the nine mutations in the spike gene in
1
this variant, there are three biologically important mutations: K417N, E484K, and
2
N501Y [7]. Importantly, there is growing evidence that the B.1.351 variant has the
3
ability to escape from the neutralizing antibody elicited against the original
4
SARS-CoV-2 infection and currently available vaccines [7, 10-12].
5
The SARS-CoV-2 variant P.1, which was first detected in Japan in early January
6
2021 from four individuals with a history of traveling to Brazil, had become the
7
predominant variant circulating in Brazil by January 2021 [13]. It bears 12 mutations in
8
the spike gene, including K417T, E484K, and N501Y [14], which are the same three
9
amino acid substitutions as those found in B.1.351. Interestingly, variant P.1 showed
10
less resistance to a neutralizing antibody induced by natural infection or vaccination
11
compared to a similar variant, B.1.351 [15].
12
The emergence of these variants poses a tremendous challenge to the control of
13
the SARS-CoV-2 pandemic. In addition, the B.1.351 and P.1 variants carry the E484K
14
mutation that is responsible for evasion from the monoclonal antibody against original
15
SARS-CoV-2, further compromising the currently available therapy against this virus
16
[16].
17
As of May 2021, Japan has experienced four waves of the COVID-19 pandemic,
18
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 13, 2021. ; https://doi.org/10.1101/2021.06.10.21258682doi: medRxiv preprint
References
More filters
Journal Article•DOI•
Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus.

[...]

Bette T. Korber1, Will Fischer1, Sandrasegaram Gnanakaran1, Hyejin Yoon1, James Theiler1, Werner Abfalterer1, Nick Hengartner1, Elena E. Giorgi1, Tanmoy Bhattacharya1, Brian T. Foley1, Kathryn M. Hastie2, Matthew Parker3, David G Partridge, Cariad Evans, Timothy M. Freeman3, Thushan I de Silva3, Adrienne Angyal4, Rebecca Brown4, Laura Carrilero4, Luke R. Green5, Luke R. Green6, Luke R. Green2, Danielle C. Groves5, Katie Johnson5, Alexander J Keeley3, Benjamin B Lindsey4, Paul J. Parsons4, Mohammad Raza, Sarah Rowland-Jones, Nikki Smith, Rachel Tucker, Dennis Wang, Matthew Wyles, Charlene McDanal4, Lautaro G. Perez4, Haili Tang4, Alex Moon-Walker6, Alex Moon-Walker2, Alex Moon-Walker5, Sean P. J. Whelan5, Celia C. LaBranche4, Erica Ollmann Saphire2, David C. Montefiori4 •
Los Alamos National Laboratory1, La Jolla Institute for Allergy and Immunology2, University of Sheffield3, Durham University4, Washington University in St. Louis5, Harvard University6
20 Aug 2020-Cell
TL;DR: A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic, and it is found that the G614 variant grows to higher titer as pseudotyped virions.

3,302 citations

Journal Article•DOI•
Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.

[...]

Quanxin Long1, Xiaojun Tang2, Qiu Lin Shi2, Qin Li3, Hai Jun Deng1, Jun Yuan1, Jie Li Hu1, Wei Xu2, Yong Zhang2, Fa Jin Lv2, Kun Su3, Fan Zhang, Jiang Gong, Bo Wu3, Xia Mao Liu2, Jin Jing Li2, Jing Fu Qiu2, Juan Chen1, Ailong Huang1 •
Laboratory of Molecular Biology1, Chongqing Medical University2, Centers for Disease Control and Prevention3
18 Jun 2020-Nature Medicine
TL;DR: A cohort of asymptomatic patients infected with SARS-CoV-2 had significantly lower levels of virus-specific IgG antibodies compared to a cohort of age- and sex-matched symptomatic infected patients.
Abstract: The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1 The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d) The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0028) The virus-specific IgG levels in the asymptomatic group (median S/CO, 34; IQR, 16-107) were significantly lower (P = 0005) relative to the symptomatic group (median S/CO, 205; IQR, 58-382) in the acute phase Of asymptomatic individuals, 933% (28/30) and 811% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 968% (30/31) and 622% (23/37) of symptomatic patients Forty percent of asymptomatic individuals became seronegative and 129% of the symptomatic group became negative for IgG in the early convalescent phase In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys

2,463 citations

Journal Article•DOI•
Effectiveness of convalescent plasma therapy in severe COVID-19 patients.

[...]

Kai Duan1, Bende Liu, Li Cesheng, Huajun Zhang2, Ting Yu, Jieming Qu3, Min Zhou3, Li Chen3, Shengli Meng, Hu Yong, Cheng Peng2, Mingchao Yuan4, Jinyan Huang3, Zejun Wang, Jianhong Yu, Xiaoxiao Gao2, Dan Wang4, Xiaoqi Yu3, Li Li, Jiayou Zhang, Xiao Wu, Bei Li2, Yanping Xu3, Wei Chen, Peng Yan, Yeqin Hu, Lin Lianzhen, Xuefei Liu3, Shihe Huang, Zhou Zhijun, Lianghao Zhang, Yue Wang, Zhang Zhi, Kun Deng, Zhiwu Xia, Gong Qin, Wei Zhang, Xiaobei Zheng, Ying Liu, Huichuan Yang1, Dongbo Zhou1, Ding Yu1, Jifeng Hou, Zhengli Shi2, Sai-Juan Chen3, Zhu Chen3, Xinxin Zhang3, Xiaoming Yang1 •
Biotec1, Chinese Academy of Sciences2, Shanghai Jiao Tong University3, Gulf Coast Regional Blood Center4
28 Apr 2020-Proceedings of the National Academy of Sciences of the United States of America
TL;DR: CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases and the optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.
Abstract: Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

1,645 citations

Journal Article•DOI•
Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7.

[...]

Pengfei Wang1, Manoj S. Nair1, Lihong Liu1, Sho Iketani1, Sho Iketani2, Yang Luo1, Yicheng Guo1, Maple Wang1, Jian Yu1, Baoshan Zhang3, Peter D. Kwong2, Peter D. Kwong3, Barney S. Graham3, John R. Mascola3, Jennifer Y Chang2, Jennifer Y Chang1, Michael T. Yin2, Michael T. Yin1, Magdalena E. Sobieszczyk2, Magdalena E. Sobieszczyk1, Christos A. Kyratsous4, Lawrence Shapiro2, Lawrence Shapiro1, Zizhang Sheng1, Yaoxing Huang1, David D. Ho1, David D. Ho2 •
Aaron Diamond AIDS Research Center1, Columbia University2, National Institutes of Health3, Regeneron4
08 Mar 2021-Nature
TL;DR: In this paper, the authors show that B.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclanal antibody against the receptor-binding domain.
Abstract: The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization1-3, and more treatments are under development4-7. Furthermore, multiple vaccine constructs have shown promise8, including two that have an approximately 95% protective efficacy against COVID-199,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.

1,641 citations

Journal Article•DOI•
Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells

[...]

Shutoku Matsuyama1, Naganori Nao1, Kazuya Shirato1, Miyuki Kawase1, Shinji Saito1, Ikuyo Takayama1, Noriyo Nagata1, Tsuyoshi Sekizuka1, Hiroshi Katoh1, Fumihiro Kato1, Masafumi Sakata1, Maino Tahara1, Satoshi Kutsuna, Norio Ohmagari, Makoto Kuroda1, Tadaki Suzuki1, Tsutomu Kageyama1, Makoto Takeda1 •
National Institutes of Health1
31 Mar 2020-Proceedings of the National Academy of Sciences of the United States of America
TL;DR: It is shown that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to Sars-CoV-2 infection, making it useful for isolating and propagating SARS-Cov-2.
Abstract: A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many countries globally. Here, we show that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.

1,139 citations

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( which was not certified by peer review ) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

Increased transmission of SARS-CoV-2 lineage 5B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway 6cells or antibody escape.